Inhibition of cartilage degradation in rat collagen-induced arthritis but not adjuvant arthritis by the neutrophil elastase inhibitor MDL 101,146.
OBJECTIVE
The neutrophil elastase inhibitor MDL 101,146 was examined for its anti arthritic effect and to determine the role of neutrophil elastase in collagen-induced arthritis and adjuvant arthritis.


METHODS
The collagen-induced arthritis model was performed in female DA rats immunized on day 0 an 1.7 with chick type II collagen in Freund's incomplete adjuvant. Adjuvant arthritis was induced in female Lewis rats by an intradermal injection of heat-killed Mycobacterium tuberculosis H37RA.


METHODS
The clinical signs of arthritis were assessed, joint swelling was measured using calipers and bone degradation, new bone proliferation, pannus formation and cartilage degradation were evaluated histologically.


RESULTS
MDL 101,146 administered orally inhibited the severity of collagen-induced arthritis as measured by a reduction in clinical score and joint swelling. Histological evaluation demonstrated a bone and cartilage sparing effect of MDL 101,146 in the tibio-tarsal joint of animals with collagen-induced arthritis.


CONCLUSIONS
These results suggest that destruction of the joint in collagen-induced arthritis is at least partially due to neutrophil elastase.
Janusz
M J
MJ
Hoechst Marion Roussel Pharmaceuticals, OH 45215, USA. michaeljanusz@hmri.com
Durham
S L
SL
D000818:Animals; D001168:Arthritis / Q000139:chemically induced* / Q000188:drug therapy*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology*; D002358:Cartilage, Articular / Q000473:pathology*; D003094:Collagen; D005260:Female; D005466:Fluorocarbons; D006614:Hindlimb / Q000473:pathology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D009025:Morpholines / Q000627:therapeutic use*; D009842:Oligopeptides / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*
D005466:Fluorocarbons; D009025:Morpholines; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; C088380:MDL 101146; D003094:Collagen; D019272:Leukocyte Elastase